Trial of Topical Selinexor (KPT-330) in Patients with Diabetic Foot Ulcers (DFU)
A Phase 1/2, Multi-Dose, Evaluator-Blinded, Randomized, Vehicle- and Standard of Care-Controlled Dose-Escalation Study to Assess Safety, Tolerability, and Pharmacokinetics of Topical Selinexor (KPT-330) in Patients with Diabetic Foot Ulcers (DFU)
Karyopharm Therapeutics Inc.
30 participants
Dec 15, 2014
Interventional
Conditions
Summary
The purpose of this research study is to see if topical (applied to the skin) selinexor has any effects towards the healing of diabetic foot ulcer(s). In non-healing diabetic foot ulcers, the wound healing process does not work properly and the ulcer is locked into a state of continued inflammation. While there are other factors that contribute to the failure of the wound to heal, controlling the state of inflammation would be beneficial for wound healing. Inflammation is controlled by multiple mechanisms within human cells. One way inflammation continues uncontrolled is when cells get rid of certain “anti-inflammatory” proteins that would normally reduce inflammation. The study drug selinexor works by trapping “anti-inflammatory proteins” within the cell, reducing inflammation so that the wound can begin to heal. Oral selinexor has previously been tested in humans to define a safe dose to be administered. The dose to be used in the topical form is more than 23,000 times lower than the oral form. This study will examine the effects of selinexor on diabetic foot ulcer(s) including any side-effects. Participation in this study could be up to 7 months involving 24 visits. Following informed consent participants enter a screening phase which includes medical history taking, physical exam, measuring vital signs & weight, eye examination, limb sensation and blood flow testing, photographs taken of the wound, electrocardiogram, blood and urine samples will be collected for standard laboratory testing. Participants will be provided instructions on how to treat their DFU. Participants will be provided with a diary and instructions on how to complete it. After the screening phase, eligible participants will be randomized to a treatment group within a sequential dose cohort. During the treatment period (up of 12 weeks) all participants will receive standard of care plus selinexor, vehicle gel or standard of care alone. Assessments will include the same done in the screening phase and additional blood samples collected for pharmacokinetic testing. After the treatment phase, participants will be asked to attend an end of treatment visit where assessments described in the treatment phase will be repeated. Finally there will be 3 follow up visits and 2 follow up phone calls over 12 weeks for those participants who have complete wound closure at the end of the treatment phase.
Eligibility
Inclusion Criteria7
- Patient is male or female 18-80 years old
- Patients with diabetes (Type I or Type II)
- Women of childbearing potential must have a negative urine pregnancy test and must agree to an effective method of contraception..
- Male patients who are sexually active with female partners who are of childbearing potential must agree to use an effective method of contraception
- Up to two anatomically discrete DFU that are non-healing but have persisted for less than or equal to 12 months
- Adequate arterial supply to the affected limb
- Inability to perceive 10 grams of pressure in the affected limb
Exclusion Criteria25
- Patient is pregnant, lactating, or is planning to become pregnant during the study.
- Patient is currently enrolled in an investigational drug or device study or has used an investigational drug or investigational device treatment within 30 days prior Patient has a foot ulcer that is clearly of non-diabetic pathophysiology.
- More than 2 DFU’s on the target limb
- DFU on the heel
- Clinically infected DFU
- Active osteomyelitis or uncontrolled connective tissue disease
- Active malignancy
- Active systemic infection
- Active Charcot foot or other structural deformity within 6 months
- Positive for HIV or Hepatitis
- Significant sickle-cell anemia or peripheral vascular disease
- Diabetic neuropathy (Grade 3 or Grade 2 with significant pain)
- End stage renal failure
- Poor nutritional status
- Any laboratory values collected in the study that is 2 times the upper limit of normal
- Revascularisation surgery within last 8 weeks
- Non-surgical peripheral revascularization within 4 weeks
- Recent surgery to affected foot within 8 weeks
- Radiation therapy to affected foot
- Systemic antibiotics, corticosteroids, supplemental vitamin E, chemotherapeutic agents, immunosuppressive drugs, antivirals angiogenesis inhibitors 2 weeks prior.
- Dermal substitute or living skin equivalent 30 days prior
- Autologous growth factor therapy 30 days prior
- Vacuum assisted closure, hyperbaric oxygen or other non-drug DFU therapy within 30 days
- Sensitivity to ingredients in study drug
- History of drug or alcohol abuse within 6 months
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
All participants will receive standard of care (SOC) treatment for their DFU. SOC treatment will include surgical debridement of the ulcer, saline rinses and dressing changes. Participants will be enrolled into one of three treatment cohorts. There will be approximately 10 participants per cohort group. In each cohort, 6 of the 10 participants will receive one of the following topical selinexor gel concentrations (10 micromolar, 30 micromolar or 70 micromolar). About 2mL of gel will be applied to a DFU twice per week for 12 weeks. All participants in the first cohort group must have completed at least 4 weeks of treatment before the next cohort group starts. Participants will be asked to return the syringes of topical selinexor gel (used and unused) at each study visit to monitor use of the topical gel. The participants will also complete a diary to record the dates and times of topical gel application.
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12614001260617